JP2009541404A5

JP2009541404A5 -

Info

Publication number: JP2009541404A5
Application number: JP2009517024A
Authority: JP
Filing date: 2007-07-02
Publication date: 2013-04-11

Claims

Heterocyclic derivatives according to formula I or pharmaceutically acceptable salts or solvates thereof

[Where:
R ¹ is C _1-4 alkyl or CN, said C _1-4 alkyl optionally substituted with 1-3 halogens;
R ² is C _1-4 alkyl, C _1-4 alkyloxy or C _1-5 acyl, wherein said C _1-4 alkyl is a substituent selected from OH, C _1-4 alkyloxy and NR ⁷ R ⁸ Optionally substituted by a group or R ² together with R ³ forms a 5- to 7-membered unsaturated carbocycle optionally containing N;
R ³ is H or methyl (optionally substituted by hydroxy or 1-3 halogen) or R ³ together with R ² is a 5- to 7-membered unsaturated carbocycle optionally containing N Forming;
R ⁴ is hydroxymethyl, CO ₂ H or CONR ⁹ R ¹⁰ ;
R ⁵ and R ⁶ are independently H, C _1-4 alkyl or C _3-8 cycloalkyl, or R ⁵ together with R ⁶ optionally includes a heteroatom moiety selected from O and NR ¹¹ Forms a 6-membered unsaturated carbocycle;
R ⁷ and R ⁸ are independently H, C _1-6 alkyl or C _3-8 cycloalkyl, said C _1-6 alkyl being optionally substituted by hydroxy, C _1-4 alkyloxy or 1-3 halogen. Or R ⁷ and R ⁸ together with N to which they are attached form a 3-6 membered saturated heterocycle;
R ⁹ is, H or _{(hydroxy, C 1-6} ^alkyloxy, optionally substituted by 1-3 groups selected from ^{^{^{NR 12 R 13, CONR 14 R}}} 15 and _{Y) C 1-4} alkyl Wherein Y is a 5-6 membered heteroaryl containing 1-2 heteroatoms selected from O, N and S, or where Y is O, S, SO ₂ and NR C _3-8 cycloalkyl optionally containing 1-2 heteroatom moieties selected from ¹⁶ and Y is selected from C _1-4 alkyl, CH ₂ OH and CH ₂ NR ¹⁷ R ¹⁸ ., which is optionally substituted by - the two substituents be); or R ⁹ is, O, _{C 3-8} is a cycloalkyl or ^{R 9} containing a hetero atom moiety selected from S and ^{NR 16} Contact Fine ^{R 10,} together with the N to which they are attached, O and NR
Forming a 5-6 membered saturated heterocycle optionally containing a heteroatom moiety selected from ¹⁶ ;
R ¹⁰ is H or methyl (provided that when R ⁹ is methyl, R ¹⁰ must be C _1-4 alkyl) or R ¹⁰ and R ⁹ are the N to which they are attached. And forms a 5-6 membered saturated heterocycle optionally comprising a heteroatom moiety selected from O and NR ¹⁶ ;
R ¹¹ is H or methyl;
R ¹² is H or C _1-4 alkyl or R ¹² and R ¹³ optionally include a heteroatom moiety selected from O, S and NR ¹⁹ with N to which they are attached 5-6 Forming a membered saturated heterocycle;
R ¹³ is H, C _1-4 alkyl, CO ₂ R ²⁰ or SO ₂ R ²⁰ or R ¹³ and R ¹² are selected from O, S and NR ¹⁹ together with N to which they are attached. Forming a 5-6 membered saturated heterocycle optionally containing a heteroatom moiety;
R ¹⁴ -R ¹⁹ is independently H or C _1-4 alkyl;
R ²⁰ is C _1-4 alkyl, and m is 1-4;
However, ^{R 1} is CF _3, when ^{R 2} together with R ^3, forms a 6 membered unsaturated carbocyclic ring, and ^{R 5} together with R ^6, to form a 6-membered unsaturated carbocycles, R ⁴ cannot be CONH ₂ . ].

Use of the heterocyclic derivative according to any one of claims 1 to 8 for the manufacture of a medicament for treating or preventing a mental illness requiring an increased synaptic response mediated by an AMPA receptor. The mental illness is neurodegenerative disorder, cognitive or memory dysfunction, memory and learning disorder, attention disorder, trauma, cerebral infarction, epilepsy, Alzheimer's disease, depression, schizophrenia, mental disorder, anxiety, Said use selected from the group consisting of autism, disorder or disease resulting from neurological agents, drug abuse, alcoholic psychosis, Parkinson's disease, narcolepsy resulting from sleep disorder or sleep deprivation or other pathological conditions .